Presently there is no imaging technology capable of detecting neuronal activity in the entire human brain with millisecond and millimeter resolution. We propose to evaluate the possibility of developing a novel noninvasive method, sonoelectric tomography (SET), capable of directly imaging electrophysiological activity in the entire human brain with such resolution. In this method, conventional scalp electroencephalography (EEG) is used to measure the electrical activity. Each location of active tissue giving rise to the EEG signals is determined from the tagged US signature in the EEG signals. This information can be used to noninvasively construct a tomographic image of neuronal currents. In order to develop such a technique, we will evaluate three candidate mechanisms: (1) acousto-electric (AE) modulation of tissue resistivity, (2) mechanical vibration of the equivalent current dipole sources in active tissue, and (3) modulation of membrane properties. At present, it is still unknown which of these mechanisms can be used to implement the SET. We will first evaluate these mechanisms in rats in vivo. In Aim 1, we will apply a focused US to one region of the barrel cortex of the rat and test the sensitivity of the SET based on each mechanism. One barrel column will be activated by single whisker stimulation and the resulting local field potentials (LFPs) on the brain or scalp will be analyzed. The most viable US-encoding scheme will be determined from the US signatures in the LFPs. Aim 2 will be very similar to Aim 1, except a single linear US beam varying in US frequency along the beam will be applied to produce a one-dimensional image of neuronal activity. Aims 1 and 2 will establish the effective and safe mechanism for developing SET for human use. In Aim 3, the five digits of a hand will be stimulated with transcutaneous electrical stimulation to activate the finger areas in areas 3b. A linear US beam will be applied to each projection area in area 3b. The scalp EEG signals in area 3b will be analyzed for presence of EEG signals at the US frequency specific for each projection site. This will identify each active site. We will test to see if this method can identiy multiple active tissues. Alternatively, we will first identify the active tissues using a whole-hea MEG and/or EEG and then use the US to test the presence of activity at each predicted site. These tests will determine the feasibility and the best direction for developing a truly whole-brai US-based Activity mapping (USAmapping) technique.